The Activity of β-Hexosaminidase (uHex) and γ-Glutamyl-Transferase (uGGT) in Urine as Non-Invasive Markers of Chronic Alcohol Abuse: I. Alcohol-Dependent Subjects

Abstract

It has been demonstrated that in alcohol-dependent men the uHex test is one of the most powerful discriminating tools, while uGGT has a discriminating power similar to that of sHex but worse than that of uHex, sGGT and s%CDT. Receiver Operating Characteristic (ROC) areas under the curves (AUC) for uHex, uGGT, s%CDT, sHex and sGGT were 0.92, 0.79, 0.88, 0.79 and 0.92, respectively. Due to their good parameters, low cost, ease of use and non-invasive character the uHex and uGGT tests are useful tools for the detection of chronic alcohol abuse.

Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse

“…The present study confirmed the results of our preliminary work on uHex utility in alcohol-dependent men (21,22), and showed negligible bias from endogenous inhibitors of the enzyme. This finding and the slightly, albeit non-significantly, higher AUC value ( Table 2) mean that uHex is superior to eAAP as a possible clinical marker.…”

“…Factor analysis of the markers studied revealed that the liver and kidney origins of the markers were independent factors, and showed significant correlation within, but not between, the two marker groups. These findings indicate that these marker groups represent metabolically unrelated events, which is in agreement with previous studies (20)(21)(22)(23) and suggests that combining representatives of these marker groups would be of diagnostic advantage. This indication was confirmed by the stepwise discriminant analysis, which showed highest diagnostic potential for the combination of GGT and uHex data into a composite marker and no significant gain from adding any of the remaining markers to this combination.…”

“…However, because of its relatively large molecular size (130-140 kDa), serum Hex should not normally be filtered through the glomeruli and contribute to urinary Hex (uHex) activity. In fact, a number of studies have revealed a lack of correlation between serum Hex and uHex in alcohol abusers (20)(21)(22). Hence, alcohol abuse-related elevation of urinary activity of Hex and AAP represents a potential tool for non-invasive diagnosis of such abuse.…”

“…This may be due to different gender, age, BMI (14,33), ethnicity, alcohol intake and incidence of tobacco smoking in different patient cohorts studied (14,34), and disparate cutoff values employed (21,22,35). Distinct drinking patterns may also be of substance, as some reports have shown ''sensitization'' after chronic heavy drinking (34,36).…”

Molecular Targets of Alcohol Action

“…The most common traditional marker is gamma-glutamyltransferase (GGT) (287). The liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are also measured as biomarkers of heavy alcohol consumption in routine screening for liver damage (288).…”